Poorly soluble active drug substances most often present problems in the manufacture of drug formulations. The water solubility is crucial for absorption and hence bioavailability in the case of the most important route of absorption, passive diffusion. In order to overcome a solubility problem, the formulator is compelled to either increase the solubility on the molecular level by creating a pro-drug or by adding solubility enhancing additives or excipients. The second alternative often includes excipients of lipophilic character like oils. In addition surface-active agents, or detergents, are added in order to create an emulsion. The created emulsion could be thermo-dynamically stable, i.e. a micro emulsion. Said formulations are mostly intended for use as wet systems as mixtures or soft gelatine capsules.
It is well known that lipophilic substances with a very low solubility in water will have a higher bioavailability when administered in a microemulsion, see for instance “Lipid micro emulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects.” Constanttinides, P. P. (1995) Pharmaceutical Research, 12, (11) 1561-1572; and “Enhanced intestinal absorption of an RGD peptide from water-in-oil micro emulsions of different composition and particle size”, Constantinides, P. P. et al., (1995) Journal of controlled release 34, 109-116; and “Lipid based vehicles for the oral delivery of poorly water soluble drugs”, Humberstone, A. J. and Charman, W. N.; (1997) Advanced Drug Delivery Reviews, 25, 103-128.
Tablets are in general the preferred dosage form, being comparatively less expensive to manufacture, easy to store and administer. There is, however, no general way to formulate poorly soluble lipophilic drug substances as tablets wherein the total lipophilic system constitutes a substantial quantity of the tablet weight. This is due to general disturbances and breakage in the interparticulate bonding forces known to be generated by lipophilic substances.